Effect of Butyrate Supplement on Rheumatoid Arthritis

A Pilot Study to Evaluate Efficacy and Safety of Butyrate Supplement in the Treatment of Rheumatoid Arthritis

This study is a pilot study to evaluate the safety and efficacy of administering butyrate supplement on rheumatoid arthritis patients. Thirty participants will be included to receive butyrate supplement for 12 weeks. Changes of immune cell subtypes, markers of intestinal damage, intestinal flora and other laboratory indicators will be monitored.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Sodium Butyrate

Detailed Description

This is a single center, uncontrolled, open-label study to assess the efficacy and safety of butyrate supplement plus standard therapy in rheumatoid arthritis(RA). The patients will be given 2 sodium butyrate capsules (containing 1200 mg of sodium butyrate) daily as supplemental therapy. The objective is to assess the effects of 12 weeks of sodium butyrate supplementation on intestinal inflammation and immune regulation in patients with RA, specifically changes in T-cell subtypes and biomarkers associated with intestinal injury. Clinical manifestations and other laboratory indices will also be monitored.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Department of Rheumatology and Immunology, Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female ≥18 years of age at the time of screening, weight≥35 kg.
• Diagnosed with rheumatoid arthritis satisfying the 1987 American College of Rheumatology classification criteria.
• Stable treatment, including DMARDs (disease-modifying anti-rheumatic drugs) and glucocorticoids, was stable in dose for at least 4 weeks, and no biological agents were used during the first 12 weeks of enrollment.
• Have given written informed consent

Exclusion Criteria:

• Patient presenting or having a history of other autoimmune diseases (such as Sjogren's syndrome, systemic lupus erythematosus, systemic sclerosis, vasculitis, etc.) and other arthritic diseases (such as spinal arthritis, psoriatic arthritis, reactive arthritis, etc.)
• Patient with ongoing or previous Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme
• Patient with significantly impaired bone marrow function or significant anemia, leucopenia or thrombocytopenia induced by other disease
• Patient with persistent or severe infection within 3 months before enrollment
• Patient with uncontrolled hypertension, uncontrolled diabetes, unstable ischemic heart disease, active inflammatory bowel disease, active peptic ulcer disease, terminal illness or other medical condition which would put the patient at risk of participating in the study according to the opinion of investigator
• Patient with cardiovascular, hepatic, neurological, endocrine, or other major systemic disease, which may make implementation of the protocol or interpretation of the study results difficult
• Patient who has severe hypoproteinemia (e.g., in case of severe liver disease or nephrotic syndrome), with serum albumin < 30 g/L)
• Patient who has moderate or severe impairment of renal function (the estimated glomerular filtration rate was < 60 mL/min/1.73 m2)
• Patient with impairment of liver function or persisting Alanine transaminase (ALT) or Aspartate aminotransferase (AST) elevations of more than 2-fold the upper limit of normal
• Patient with Known HIV positive status or positive serology for hepatitis B or C
• Pregnant or breastfeeding woman
• Women of childbearing potential
• Men wishing to father children during the course of the study or within the 24 months thereafter (or 3 months with the washout procedure)
• Patient with a congenital or acquired severe immuno-deficiency, a history of cancer or lymphoproliferative disease, or any patient who has received total lymphoid irradiation.
• Patient who enrolled in any other clinical trial involving off-label use of an investigational drug or device, or any other type of medical research
• Patient using any biologic agent such as anti-tumor necrosis factor, IL-6 receptor antagonist, anti-CD20 monoclonal antibody within 3 months prior to the first dose of treatment.
• Patient whose BMI (body mass index) is under 18.5 kg/m2 or more than 30 kg/m2
• Patient with history of drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Butyrate supplement; 2 capsules butyrate supplement (containing 1200 mg of butyric acid ) once a day for 12 weeks Drug: sodium butyrate	Drug: Sodium Butyrate; 2 capsules butyrate supplement once a day for 12 weeks; Other Names: TRI-Butyrin Supreme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in disease Activity Score in 28 joints (DAS28)	Evaluating changes in DAS28 before and after treatment. DAS28 was calculated by the number of swollen joints (SJC) and tender joints (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (mm/h) or c-reactive protein (CRP) (mg/L), and patient's global assessment (PGA) of disease activity (based on the visual analog score [VAS], 0-100mm). Compared with the baseline, a lower DAS28 would mean an improvement in disease activity. Conversely, an increase in DAS28 indicates a deterioration in disease activity.	Baseline,12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the simplified disease activity index (SDAI)	Evaluating changes in SDAI before and after treatment. The SDAI is a composite score based on the tender joints of 28 joints (TJC28), tender joints of 28 joints (SJC28), patients' and physicians' global assessments of disease activity (based on the visual analog score [VAS], 0-10cm), and c-reactive protein (CRP). Compared with the baseline, a lower SDAI would mean an improvement in disease activity. Conversely, an increase in SDAI indicates a deterioration in disease activity.	Baseline and 12 weeks
Changes in the clinical disease activity index (CDAI)	Evaluating changes in CDAI before and after treatment. The Clinical Disease Activity Index (CDAI) is a composite score based on the TJC28, SJC28, and patients'and physicians'assessments (based on the visual analog score [VAS], 0-10cm). Compared with the baseline, a lower CDAI would mean an improvement in disease activity. Conversely, an increase in CDAI indicates a deterioration in disease activity.	Baseline and 12 weeks
Changes in T cell subtypes.	Evaluating changes in the percentage of T cell subtypes, especially T regulatory cells, in peripheral blood before and after treatment.	Baseline, 4 weeks and 12 weeks
Changes in c-reactive protein (CRP).	Evaluating changes in concentration of CRP (mg/L) before and after treatment.	Baseline, 4 weeks and 12 weeks
Changes in erythrocyte sedimentation rate (ESR).	Evaluating changes in concentration of ESR (mm/h) before and after treatment.	Baseline, 4 weeks and 12 weeks
Changes in serum lipopolysaccharide-binding protein (LBP)	Evaluating changes in LBP concentration in serum before and after treatment.	Baseline, 4 weeks and 12 weeks
Changes in serum intestinal fatty acid-binding protein (I-FABP)	Evaluating changes in I-FABP concentration in serum before and after treatment.	Baseline, 4 weeks and 12 weeks
Changes in serum soluble cluster of differentiation 14 (sCD14)	Evaluating changes in sCD14 concentration in serum before and after treatment.	Baseline, 4 weeks and 12 weeks
Numbers of participants with treatment-related adverse events	Adverse effects include fever, rash, abnormal liver and kidney function, new-onset infection, and any abnormal measures associated with experimental drugs.	12 weeks

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Zhanguo Li, Peking University Institute of Rheuamotology and Immunology

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2022
• Primary Completion (Actual): October 1, 2023
• Study Completion (Actual): June 15, 2024

Study Registration Dates

• First Submitted: October 7, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 20, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Histamine Antagonists; Histamine Agents; Butyric Acid
• Other Study ID Numbers: ButyrateRA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No